The objective of this project is the development of a model system for studying the way in which specific maternally-produced components of the egg cytoplasm regulate gene expression during early embryonic growth. Toward this end I propose to study the genetic, developmental, and molecular interactions that are responsible for the female-specific, lethal maternal effect of the daughterless (da) mutation of D. melanogaster. I anticipate that this system will be useful for understanding the nature of the self-sustaining genetic changes that are involved in the determination of cell fates. In the course of my work with the autosomal da mutation, I isolated a strong supressor of da ( Su(da) ) that maps to the Female lethal (Fl) locus on the X chromosome. I propose an extensive genetic and developmental characterization of the da, Su(da) and Fl loci which I believe will indicate the basis for the sex-specific action of the da maternal effect, and will lead to a comprehensive model for the da mutant's complex phenotype. This work will include the analysis of: double mutants, gene dosage effects, new mutant alleles, recombination frequencies, effects on embryonic morphology, genetic mosaics, and mutant tissue transplantation. Analysis of events at the molecular level is possible with this mutant. A bioassay for the component of the egg cytoplasm that is responsible for the da maternal effect has been developed and will be used to determine: (1) when during oogenesis the specific activity of the factor is highest; (2) how stable the factor is; (3) what fraction of the cytoplasm contains the factor; and (4) from what other sources the factor can be obtained. This work will be preparatory to an investigation of the molecular nature of this cytoplasmic regulatory factor. In addition, some effort will be directed towards understanding the nature of the early gene product whose synthesis appears to be stimulated by the da positive maternal factor.